Aspergillus spp., notably Aspergillus fumigatus, may cause life-threatening infections among transplant recipients and patients receiving therapy for various types of cancer. The most commonly encountered form of disease in these patients is pulmonary aspergillosis (1). Acute fatal sinusitis (2, 3), head and neck involvement (4), cutaneous disease (5) and catheter related infections (6) have also been described.
Invasive pulmonary aspergillosis is difficult to diagnose, even with invasive techniques. Therefore the standard treatment, intravenous amphotericin B, often has to be given empirically--despite its severe toxicity and despite the fact that patients do not tolerate it well. Moreover, amphotericin B is not always effective, and correction of the underlying disorder (e.g. resolution of granulocytopenia) is usually required to achieve a favorable outcome.
In one study involving seven subjects with pulmonary aspergillosis, Ikemoto, et al reported that the treatment of choice in patients with repeated episodes of haemoptysis is surgical excision (33). The authors also reported that treatment with amphotericin B by aerosol inhalation in two patients was unsuccessful, probably because the drug could not reach the apex of the lung in this form.
It has also been reported that treatment of invasive pulmonary aspergillosis was successful using a combination of amphotericin B and 5-flurocytosine administered intravenously and by inhalation (32, 34).
In a study of distribution and activity of amphotericin B in humans, found the highest concentrations of drug was found in the liver, spleen and kidneys (7). Concentrations above 7 mcg per gram of lung tissue were only seen in patients who had received at least 1.7 g of amphotericin B. This data also suggested, that once amphotericin B accumulated in any organ, it was eliminated slowly.
It is assumed, that a reduction of the number of aspergillus spores inhaled, can reduce the risk of developing invasive aspergillus pneumonia among susceptible hosts (8, 9, 10, 11). Amphotericin B is highly fungicidal against aspergillus spores (12), and has a long half life once it reaches the lung parenchyma.
In a newly developed rat model for pulmonary aspergillosis (13) aerosol amphotericin B (aero-AmB) given as prophylaxis (given once, 48 hours prior to infection) or as therapy (given 24 hours after infection, then daily for six days) was evaluated to determine whether had an influence on survival. Other studies were done to determine the pulmonary deposition and fungicidal activity of the drug after aerosol administration.